Drug & supplement interaction

Tianeptine + Pregabalin

Pregabalin brand names: Lyrica, Lyrica CR.

Moderate Interaction
The bottom line Moderate

Tianeptine has a moderate interaction with Pregabalin. Tianeptine has sedative effects; high doses may have additive effects with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Tianeptine and Pregabalin

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CNS DEPRESSANTS

Why this applies to Pregabalin

Pregabalin falls under CNS DEPRESSANTS — the group Tianeptine interacts with.

Tianeptine has sedative effects; high doses may have additive effects with other CNS depressants.
Higher doses of tianeptine have opioid like effects and may have additive effects with other sedative drugs. In one case report, a 42-year-old male presented with respiratory depression and aspiration pneumonia due to concomitant use of high-dose tianeptine and alprazolam.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with Lyrica (pregabalin) and tianeptine. Pregabalin already slows down your central nervous system, which is how it eases nerve pain but also why it can leave you drowsy, dizzy, foggy, or unsteady on your feet. Tianeptine is sedating too, and at higher doses it behaves like an opioid. Stack the two and those calming effects can pile up, meaning more sleepiness, slowed thinking, and in a worst case, slowed or shallow breathing.

This concern is based on how these substances act rather than solid studies in people, so it's theoretical, but the risk isn't trivial given tianeptine's opioid-like punch at high doses. Pregabalin doesn't need an enzyme to 'switch on,' so this is about overlapping sedation, not changed drug levels. Please loop in your doctor or pharmacist before combining them.

References
  1. Lauhan R, Hsu A, Alam A, Beizai K. Tianeptine Abuse and Dependence: Case Report and Literature Review. Psychosomatics. 2018;59(6):547-553. PubMed
  2. Lucaj S, Leo RJ. Tianeptine Sodium: A Nootropic With Potentially Lethal Consequences. Prim Care Companion CNS Disord. 2018;20(4).
  3. Samuels BA, Nautiyal KM, Kruegel AC, et al. The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor. Neuropsychopharmacology. 2017;42(10):2052-2063. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Tianeptine Also Interacts With Other Medications

Tianeptine has 9 major, 267 moderate known drug interactions in our database — the Pregabalin one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Tianeptine

Covers the 2,830 medications we’ve checked against Tianeptine. Pick one to open its full report.

From our Q&A

Questions About Tianeptine or Pregabalin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Tianeptine or Pregabalin, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Pregabalin

This page covers Tianeptine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Pregabalin page lists 95 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 7 major · 73 moderate · 15 minor.

From our pharmacist’s overview on the Pregabalin page

“Pregabalin (Lyrica) calms overactive nerves, which is how it eases nerve pain, seizures, and anxiety, and that calming action stacks with almost everything on this list. Of the 95 supplements and herbs, the large majority add their own sedation on top of pregabalin's, and a few can tip that into genuine danger, with deep sedation and s…”

Reviewed by 2 · Jul 18, 2026

Open the Pregabalin interaction page

How much people look this up

Where Tianeptine and Pregabalin Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Tianeptine
Steady interest

#1,047 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Pregabalin
Top 5%

#40 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Tianeptine

What is Tianeptine?

  • Depression (prescription use in some countries)
  • Anxiety
  • Mood enhancement
  • Pain relief
  • Self-treatment of opioid withdrawal
  • Recreational euphoria

Tianeptine is a prescription antidepressant in some countries, but it is NOT approved by the FDA in the United States and is illegally sold in dietary supplements and 'gas station' products. At high doses it acts like an opioid and carries serious risks of addiction, overdose, and dangerous withdrawal. We strongly advise against using over-the-counter tianeptine products and urge anyone considering it to talk with a doctor or pharmacist first.

Read the full Tianeptine monograph & all interactions
Medication

About Pregabalin

What Is Pregabalin Used For?

Brand names: Lyrica, Lyrica CR

Pregabalin is used to manage several types of nerve pain, including neuropathic pain from diabetic peripheral neuropathy (nerve damage caused by diabetes) and postherpetic neuralgia (lingering nerve pain after shingles). It is also used to treat fibromyalgia and neuropathic pain associated with spinal cord injury.

Lyrica (capsule and oral solution), pregabalin capsules, and pregabalin oral solution are also approved as add-on therapy for partial-onset seizures — Lyrica for patients 1 month and older, and pregabalin capsules for patients 17 years and older. Lyrica CR and pregabalin extended-release tablets are approved only for diabetic peripheral neuropathy pain and postherpetic neuralgia — their effectiveness for fibromyalgia or as seizure add-on therapy has not been established.

See full Pregabalin drug information
Keep checking

Other Drugs & Tianeptine

Browse every other medication we’ve checked against Tianeptine — both the ones with a known interaction and the ones without. Select any drug for the full detail.

9Major
267Moderate
0Minor
2,553No known interaction
Major

9 interactions

Moderate

267 interactions

Showing 60 of 267 moderate interactions — see all 267 on the Tianeptine page.

No interaction 2,553 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Tianeptine and Pregabalin Together: Common Questions

Can you take Tianeptine with Pregabalin?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Tianeptine and Pregabalin interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.